肉桂醛纳米乳的制备及体内药动学评价

Preparation and pharmacokinetic evaluation of cinnamaldehyde nanoemulsion

目的 构建肉桂醛纳米乳(Cin-NE),以提高肉桂醛(Cin)稳定性、溶解度以及口服生物利用度。方法 将Cin同时作为药物和油相,以蓖麻油聚氧乙烯醚(EL-35)为乳化剂,构建Cin乳剂(Cin-E),稀释后得到具有抗稀释性的纳米递送系统——Cin-NE,通过激光粒度仪对其粒径和PDI进行检测,采用UPLC对纳米乳中肉桂醛含量进行检测,以外观性状、粒径和含量为指标,考察长期放置的Cin-NE的稳定性。此外,通过对SD大鼠进行口服灌胃给药,研究该纳米乳的口服吸收情况以及体内药动学特征。结果 将Cin载入纳米乳中,显著提高了药物在水中的溶解度;Cin-E中Cin含量为90.9 mg/ml,其制备的Cin-NE粒径较小且分布均匀,在水、模拟胃液和模拟肠液中具有抗稀释性;4℃下放置稳定性良好。SD大鼠口服灌胃给药的体内药动学结果表明,Cin-NE生物利用度是Cin原料药的3倍,可见纳米乳显著改善了Cin的口服吸收。结论 成功构建了无需额外加入其他油相、无需助乳化剂、处方精简、工艺简单的Cin纳米药物递送系统Cin-NE,其稳定性、溶解度以及口服生物利用度显著优于Cin,为Cin的临床应用提供了有益的探索和启示。

Objective To prepare cinnamaldehyde nanoemulsion(Cin-NE)for improving the stability,water-solubility and oral bioavailability of cinnamaldehyde.Methods Cinnamaldehyde was used as both drug and oil phases,and cremophor EL-35 was used as emulsifier to construct cinnamaldehyde emulsion(Cin-E),which was diluted to obtain the nano delivery system with anti dilution property,Cin-NE.The particle size and PDI of Cin-NE was measured by laser particle sizer,and the cinnamaldehyde content of Cin-NE was examined using UPLC to investigate the stability of Cin-NE obtained from Cin-E stored for a long period of time,using appearance properties,particle size and content as indicators.In addition,the oral absorption and in vivo pharmacokinetic characteristics of Cin-NE were explored by intragastric administration in SD rats.Results The loading of cinnamaldehyde into the nanoemulsion significantly improved the solubility of the drug in water.The content of Cin in Cin-E was 90.9 mg/ml,and the particle size of its prepared Cin-NE was small and uniformly distributed,which also exhibits anti-dilution property in water,SGF and SIF.The stability of Cin-NE obtained from Cin-E stored at 4℃was good.In vivo pharmacokinetic results of SD rats administered by oral gavage showed that the bioavailability of Cin-NE was 3 times that of the raw drug,which shows that the nanoemulsion significantly improved the oral absorption of cinnamaldehyde.Conclusion By using cinnamaldehyde itself as both drug and oil phases,without additional oil phases or co-emulsifiers,Cin-NE,a cinnamaldehyde nano drug delivery system with streamlined prescription and simple process,was successfully constructed.Cin-NE significantly improved the stability,solubility,and oral bioavailability of cinnamaldehyde compared with the raw drug,providing useful exploration and insights for the clinical application of cinnamaldehyde.